rs1538687

Variant names:

• chr1-196428645-C-T
• rs1538687
• NM_198503.5:c.820-376G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198503.5(KCNT2):​c.820-376G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,868 control chromosomes in the GnomAD database, including 29,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (29856 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• Publications: 6 publications found

Genes affected

KCNT2 (HGNC:18866): (potassium sodium-activated channel subfamily T member 2) Enables chloride-activated potassium channel activity. Involved in potassium ion export across plasma membrane. Located in plasma membrane. Implicated in developmental and epileptic encephalopathy 57. [provided by Alliance of Genome Resources, Apr 2022]

KCNT2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 57

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.820-376G>A		intron_variant	Intron 9 of 27	ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.820-376G>A		intron_variant	Intron 9 of 27	1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94009 AN: 151750 Hom.: 29838 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.619 AC: 94073 AN: 151868 Hom.: 29856 Cov.: 32 AF XY: 0.618 AC XY: 45870 AN XY: 74204

African (AFR) AF: 0.470 AC: 19459 AN: 41420

American (AMR) AF: 0.620 AC: 9450 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3412 AN: 5136

South Asian (SAS) AF: 0.688 AC: 3314 AN: 4816

European-Finnish (FIN) AF: 0.654 AC: 6909 AN: 10558

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47168 AN: 67918

Other (OTH) AF: 0.645 AC: 1361 AN: 2110

Alfa AF: 0.648 Hom.: 11652

Bravo AF: 0.612

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1538687; hg19: chr1-196397775; COSMIC: COSV54070840; COSMIC: COSV54070840;